Pioneers in several countries shed light on germs, enabling important insights in the prevention and treatment of infectious disease

In May 1847 Jakob Kolletschka, a Viennese doctor, cut his finger while doing an autopsy on a woman who had died of puerperal fever in the city's lying-in hospital. A few days later Kolletschka was dead. His autopsy showed features identical to those found in puerperal sepsis. His friend Ignaz Semmelweis concluded that the disease was being carried on the hands of medical students to the women in labour and insisted that medical students should wash their hands before attending deliveries. Mortality from puerperal sepsis among patients who came into contact with the students fell from 12% to 2%. By general consent Semmelweis had, through his action, turned the germ theory of disease into clinical reality.

Although Semmelweis is credited with being the first to recognise the clinical implications of the germ theory, the existence of particles as the cause of disease had been suspected since Roman times, and germs had actually been seen by Antonie van Leeuwenhoek in the 17th century. Indeed, when the lying-in hospital was opened in 1784 no autopsies were carried out because the director, Lucas Boer, apparently foresaw the danger of infection. In 1823 Boer's successor introduced autopsies for the purpose of teaching. The hospital had two clinics: medical students worked in the first clinic, and the second clinic was used for training midwives. Midwives did not participate in autopsies, and mortality from infection was much lower in their clinic. Recognising the importance of this disease pattern, Semmelweis took action that seems obvious to modern eyes but was far from accepted in Vienna at the time.

Overcoming initial scepticism

Semmelweis's work influenced Joseph Lister, working in Glasgow. Lister was probably also influenced by his father, Joseph Jackson Lister, a Quaker wine merchant, who invented the bichromatic microscope (which uses reflected and transmitted light). This itself was an important event in medical history and possibly meant that Lister was alert to the idea of micro-organisms causing disease. Lister introduced antisepsis to his surgical practice. He was aware that carbolic acid was used to treat sewage, and he concluded that the same microbes that caused wound putrefaction might be killed through use of carbolic acid solutions to dress wounds. He also insisted that instruments and surgeons' hands should be washed with the solution. Mortality from compound fractures fell in his wards as a result of these measures.

Neither in Vienna nor in Glasgow did these innovations meet with approval. Semmelweis left Vienna in 1850 to return to his native Hungary, after the Viennese establishment refused to accept his approach as scientifically valid. Similarly Lister failed to gain the support of the managers of the Glasgow Royal Infirmary for his antisepsis techniques. They argued, with some evidence to support their case, that surgical patients' nutritional state was more important to the outcome of surgery than antisepsis and refused to implement his recommendations. Lister left Glasgow for the chair of surgery in Edinburgh. The scientific basis for the germ theory was eventually universally accepted after Koch's demonstration that infectious agents transmitted disease, Pasteur's studies of the metabolism of micro-organisms, and ultimately Fleming and others' work leading to the production of antibiotics and new ways to treat infection.

These insights into the prevention and treatment of infectious disease produced an epidemiological transition. They moved us from a society at the end of the 19th century in which infection typically caused 30% of all deaths to one at the end of the 20th in which less than 4% of deaths were due to infection. In 1900 one death in every 120 in the United States was due to infection—40% of them in children aged under 5 years. By 1980 mortality from infectious disease had declined in the US to 36 deaths in every 100 000, and life expectancy had increased by around 30 years. The fall in childhood mortality had a profound effect on family size and fertility. Advances in our understanding of hygiene, sanitation, and pathology that followed the development of germ theory have done more to extend life expectancy and change the nature of society than any other medical innovation.

In 2000 Life magazine published its list of the 100 most important advances of the previous millennium. It concluded that Gutenberg's invention of the printing press was the most important, followed by the discovery of the New World. The germ theory, at number six, was the only medical advance to make it into the top 10.

Had the germ theory not emerged as an explanation for the common causes of death in the 19th century, it is hard to imagine that these major killers would have been overcome in any other way. Admittedly, Jenner had described variolation independently of the work of Semmelweis and Lister. Had antibiotics not emerged as a treatment for bacterial disease, we might have been forced to explore enhancements of the immune system as a way to defeat infection. However, it is unlikely that such profound societal benefit brought about by our grasp of microbiological science would have been achieved in any other way.

Relearning old lessons

So what remains to be done? The systematic application of existing knowledge will yield many more advances. The developing world needs access to the sanitation and public health advances that have been so successful elsewhere. Research into infections such as HIV and malaria has to continue and expand. We need to improve our systems of surveillance and our understanding and detection of microbiological genetic mutation. We also need to continue research and to develop new ways to control infection. Perhaps the most depressing task that remains before us is to continually restate the lesson Semmelweis taught his medical students 160 years ago. Doctors and other healthcare workers are failing to wash their hands before contact with patients, and such failure is still costing lives. Resistance to the simple but lifesaving 19th century innovations remains alive and well in the 21st century.

Footnotes

Publication of this online supplement is made possible by an educational grant from AstraZeneca